职业性急性乙酸甲酯中毒患者血浆代谢组学研究  

Metabolomics study on occupational acute methyl acetate poisoning using patient plasma

作　　者：秦亦如 马安萍 丘静静 韩颖 吴家韵[1,3] 谢佐菲 孙杨乐 黄钧宜 董明 戎伟丰[1] 吴邦华[1] 胡世杰[1] QIN Yiru;MA Anping;QIU Jingjing;HAN Yin;WU Jiayun;XIE Zuofei;SUN Yangle;HUANG Junyi;DONG Ming;RONG Weifeng;WU Banghua;HU Shijie(不详;Guangdong Province Hospital for Occupational Disease Prevention and Treatment,Guangzhou,Guangdong 510300,China)

机构地区：[1]广东省职业病防治院,广东广州510300 [2]山西医科大学公共卫生学院,山西太原030001 [3]广东药科大学公共卫生学院,广东广州510300 [4]广州医科大学公共卫生学院,广东广州511436

出　　处：《中国职业医学》2023年第2期127-132,共6页China Occupational Medicine

基　　金：广东省医学科学技术研究基金项目(A2022013);广州市科技计划(2023A04J2471);广东省职业病防治院重点科研课题青年项目(Z2022-11)。

摘　　要：目的采用非靶向代谢组学技术探究职业性急性乙酸甲酯中毒患者血浆内源性代谢谱的异常。方法采用判断抽样方法,选择6例职业性急性乙酸甲酯中毒患者为中毒组,10名无职业性化学有害因素接触史的同行业健康工人为对照组。采用超高效液相色谱-四级杆飞行时间质谱法检测2组人群的血浆代谢物,进行非靶向代谢组学分析。采用主成分分析法和偏最小二乘法判别分析进行比较,寻找差异代谢物并分析其代谢通路。结果中毒组人群血浆代谢物谱与对照组人群比较差异有统计学意义。中毒组患者血浆中共筛选出195种差异表达代谢物;其中,119种表达上调,76种表达下调;脂类物质(脂质和脂质样分子)占比最高,为21.5%。与对照组比较,中毒组患者血浆中的差异代谢物富集于叶酸生物合成、氨基酸代谢、嘧啶代谢和鞘脂生物合成等代谢通路(P值均<0.05)。结论职业性急性乙酸甲酯中毒扰乱了机体的代谢;叶酸生物合成、氨基酸与脂质代谢等通路可能参与了中毒的发生发展。Objective To investigate the specificity of endogenous metabolic profile in plasma of patients with occupational acute methyl acetate poisoning using non-targeted metabolomics.Methods A total of six patients with occupational acute methyl acetate poisoning were selected as the poisoning group,while 1o healthy workers without occupational exposure history of chemical hazards in the same industry were selected as the control group using the judgment sampling method.Metabolites in patient plasma of the two groups were detected using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry,and non-targeted metabolomics analysis was performed.Principal component analysis and partial least squares discriminant analysis were used to identify differential metabolites and analyze their metabolic pathways.ResultsThere were significant differences in metabolite profiles in patient plasma between poisoning group and control group.A total of 195 differentially expressed metabolites were screened in plasma of patients in poisoning group,including 119 upregulated and 76 downregulated metabolites.Lipid substances(lipids and lipid-like molecules)accounted for the highest proportion(21.5%).The differential metabolites of poisoning group were related to folate biosynthesis,amino acid metabolism pyrimidine metabolism,sphingolipid biosynthesis and other metabolic pathways in plasma compared with the control group(all P<0.05).Conclusion Occupational acute methyl acetate poisoning affects metabolism of the body.The folic acid biosynthesis,amino acid and lipid metabolism and other pathways may be involved in the occurrence and development of poisoning.

关 键 词：乙酸甲酯 急性中毒 血浆 代谢组学 脂类 叶酸 氨基酸 代谢通路 

分 类 号：R135.1[医药卫生—劳动卫生]